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Endometrial carcinoma (EC) is a kind of fatal female malignancy. lncRNA GATA3-AS1 has been identified as an oncogene in various cancers. However, the functions and mechanisms of GATA3-AS1 in EC remain to be explored. Human EC tissues and four EC cell lines were used. Western blotting and quantitative real-time PCR (qRT-PCR) were used to evaluate the expression of GATA3-AS1, miR-361, and ARRB2. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction among GATA3-AS1, miR-361, and ARRB2. Flow cytometry, colony formation assay, scratch assay, and transwell assay were used to examine the cell apoptosis, proliferation, migration, and invasion of EC cells, respectively. In vivo tumor growth was monitored in nude mice. GATA3-AS1 and ARRB2 were upregulated while miR-361 was downregulated in human EC tissues and EC cells. GATA3-AS1 knockdown constrained cell proliferation, invasion, migration, and EMT while promoting the apoptosis of EC cells by upregulating miR-361. GATA3-AS1 negatively regulated miR-361 expression. ARRB2 was the direct target of miR-361 and could activate the Src/Akt pathway. In vivo, GATA3-AS1 knockdown suppressed tumor progression by upregulating the miR-361 expression. lncRNA GATA3-AS1 promoted EC invasion and migration by the miR-361/ARRB2 axis, which indicated that GATA3-AS1 might be a promising therapeutic option for advanced EC progression. KEY MESSAGES: GATA3-AS1 knockdown suppressed EC proliferation, invasion, and migration. GATA3-AS1 directly inhibited miR-361 as a ceRNA. MiR-361 knockdown reversed the tumor suppressive effect caused by GATA3-AS1 knockdown. MiR-361 bound to ARRB2 directly and suppressed its expression. The GATA3-AS1/miR-361/ARRB2 axis regulated EC cell proliferation, invasion, and migration.

Osteons are composed of concentric lamellar structure, the concentric lamellae are composed of periodic thin and thick sub-lamellae, and every 5 sub-lamellae is a cycle, the periodic helix angle of mineralized collagen fibers in two adjacent sub-lamellae is 30°. Four biomimetic models with different fiber helix angles were established and fabricated according to the micro-nano structure of osteon. The effects of the fiber periodic helical structure on impact characteristic and energy dissipation of multi-layer biomimetic composite were investigated. The calculation results indicated that the stress distribution, contact characteristics and fiber failur during impact, and energy dissipation of the composite are affected by the fiber helix angle. The stress concentration of composite materials under external impact can be effectively improved by adjusting the fiber helix angle when the material composition and material performance parameters are same. Compared with the sample30, the maximum stress of sample60 and sample90 increases by 38.1% and 69.8%, respectively. And the fiber failure analysis results shown that the model with a fiber helix angle of 30° has a better resist impact damage. The drop-weight test results shown that the impact damage area of the specimen with 30° helix angle is smallest among the four types of biomimetic specimens. The periodic helical structure of mineralized collagen fibers in osteon can effectively improve the impact resistance of cortical bone. The research results can provide useful guidance for the design and manufacture of high-performance, impact-resistant biomimetic composite materials.

In experimental control of quantum systems, the precision is often hindered by imperfect applied electronics that distort pulses delivered to target quantum devices. To mitigate such error, the deconvolution method is commonly used for compensating the distortion via a convolutional model. However, its effectiveness is limited by model inaccuracies (e.g., imprecise parameters or unmodeled distortion dynamics). In this article, we propose a learning-based scheme to eliminate the residual calibration error by repeatedly applying the deconvolution operations. The resulting iterative deconvolution method is shown by simulation examples to be able to correct both linear and nonlinear model errors to the highest precision allowed by available finite sampling rates, and the intersampling error caused by finite sampling rate can be suppressed by actively introducing nonlinear components in the control electronics. The proposed method is also experimentally applied on a superconducting platform, which demonstrates improved performance than the noniterative deconvolution methods.

Transcription factor aryl hydrocarbon receptor (AhR) can enhance insect resistance to insecticides by regulating the detoxification metabolic network. Our previous studies have confirmed that overexpression of cytochrome P450 monooxygenases (P450s) and glutathione S-transferases (GSTs) are both involved inlambda-cyhalothrin resistance inCydia pomonella. In this study, we report that AhR regulates GSTs thus conferringlambda-cyhalothrin resistance inC. pomonella. Spatiotemporal expression patterns indicated thatAhRgene ofC. pomonella(CpAhR) was highly expressed in the Malpighian tubules of larvae. Moreover, the expression ofCpAhRwas induced bylambda-cyhalothrin exposure and was up-regulated in alambda-cyhalothrin-resistant population. RNA interference (RNAi) of the expression ofCpAhRcould effectively decrease the relative expression level ofCpGSTe3and enzyme activity of GSTs, but not P450s, further reducing the tolerance of larvae tolambda-cyhalothrin. Furthermore, β-naphthoflavone (BNF), a novel agonist of AhR, can effectively increase the expression ofCpAhRand the activity of the GSTs enzyme, resulting in the enhancement of larvae tolerance tolambda-cyhalothrin. These results demonstrate thatlambda-cyhalothrin exposure can effectively activate the expression ofCpAhRand increase GSTs enzyme thus leading to the development of resistance tolambda-cyhalothrin, which enriches the theory of insecticide resistance regulation inC. pomonella.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a severe complication of liver surgery in hepatocellular carcinoma (HCC) patients. Reduced lean body mass (LBM) decreases the immune activity and increases adverse clinical outcomes among cancer patients. OBJECTIVE: We aimed to assess the association between LBM and PHLF in HCC patients. METHODS: PHLF was defined and graded based on the International Study Group of Liver Surgery (ISGLS) criteria. Patients with Grade B or Grade C were included in PHLF ⩾ Grade B group, while others in PHLF < Grade B group. LBM was measured via preoperative computed tomography images. Binary logistic regression was applied for investigating the association between LBM and PHLF. The receiver operating characteristic curve was used to identify potential cut-off values and assess the predictive ability of the measured variables. RESULTS: The PHLF ⩾ Grade B group had significantly lower LBM levels (means ± standard deviation: 57.0 ± 14.1) than PHLF < Grade B group (67.2 ± 15.7) (p< 0.001). After controlling other variables, LBM was an independent protective factor for PHLF ⩾ Grade B (Odds Ratio: 0.406, 95% confidence interval: 0.172–0.957, p= 0.039). The prevalence of PHLF ⩾ Grade B in each quartile of LBM was 29.4% (15/51), 25.5% (13/51), 19.2% (10/52) and 4.0% (2/50), respectively (ptrend< 0.001). CONCLUSIONS: LBM might be a protective factor for PHLF in HCC patients. Our findings might help to develop a novel strategy to reduce the occurrence of hepatic dysfunction following major liver resection. Multicentric prospective studies and further molecular biologic investigation are needed.

Quantum state transfer is one of the basic tasks in quantum information processing. We here propose a theoretical approach to realize arbitrary entangled state transfer through a qubit chain, which is a class of extended Su-Schrieffer-Heeger models and accommodates multiple topological edge states separated from the bulk states. We show that an arbitrary entangled state, from $2$-qubit to $\mathcal{N}$-qubit, can be encoded in the corresponding edge states, and then adiabatically transferred from one end to the other of the chain. The dynamical phase differences resulting from the time evolutions of different edge states can be eliminated by properly choosing evolution time. Our approach is robust against both the qubit-qubit coupling disorder and the evolution time disorder. For the concreteness of discussions, we assume that such a chain is constructed by an experimentally feasible superconducting qubit system, meanwhile, our proposal can also be applied to other systems.

BACKGROUNDThe evolution of insect resistance to pesticides poses a continuing threat to sustainable pest management. While much is known about the molecular mechanisms that confer resistance in model insects and few agricultural pests, far less is known about fruit pests.RESULTSHere we found that functional redundancy and preference of metabolism by cytochrome P450 monooxygenases (P450s) genes in the CYP9A subfamily confer resistance to lambda-cyhalothrin in Cydia pomonella, a major invasive pest of pome fruit. A total of four CYP9A genes, including CYP9A61, CYP9A120, CYP9A121, and CYP9A122, were identified from C. pomonella. Among these, CYP9A120, CYP9A121, and CYP9A122 were predominantly expressed in the midgut of larvae. The expression levels of these P450 genes were significantly induced by LD10 of lambda-cyhalothrin and were overexpressed in a field-evolved lambda-cyhalothrin resistant population. Knockdown of CYP9A120 and CYP9A121 by RNA-mediated interference (RNAi) increased the susceptibility of larvae to lambda-cyhalothrin. In vitro assays demonstrated that recombinant P450s expressed in Sf9 cells can metabolize lambda-cyhalothrin, but with functional redundancy and divergence through regioselectivity of metabolism. CYP9A121 preferred to convert lambda-cyhalothrin to 2′-hydroxy-lambda-cyhalothrin, whereas CYP9A122 only generated 4′-hydroxy metabolite of lambda-cyhalothrin. Although possesses a relatively low metabolic capability, CYP9A120 balanced catalytic competence to generate both 2′- and 4′-metabolites.CONCLUSIONCollectively, these results reveal that metabolic functional redundancy of three members of the CYP9A subfamily leads to P450-mediated lambda-cyhalothrin resistance in C. pomonella, thus representing a potential adaptive evolutionary strategy during its worldwide expansion.

The codling moth Cydia pomonella (Lepidoptera: Tortricidae) is a major invasive pest of pome fruits and walnuts worldwide. Lambda-cyhalothrin (LCT) and abamectin (AM) have been frequently used in C. pomonella control, but control of this pest is very difficult because shortly after hatching, larvae of this insect bore tunnels and hide inside host plant fruit. In this study, a simulated field spray bioassay method was developed against neonate larvae of C. pomonella and concentration-response bioassays were conducted to evaluate the susceptibility of the neonate larvae to LCT and AM. Exposure of neonate larvae to sublethal concentrations (LC30) of LCT or AM significantly reduced the survival rate of larvae (4th and 5th instars), lowered the mean weight of larvae and pupae, and decreased the daily maximal number of eggs laid and the total number of eggs laid (fecundity) per female. The sublethal effects, including reduced body mass, mean fecundity and net reproductive rate, extended mean generation time, and shortened oviposition period, were also found in transgenerational offspring. Furthermore, the transgenerational maternal effects were more obvious for AM than LCT, in comparison to the control. Additionally, the estimated population size was decreased by exposure to LC30 of LCT and AM, and the observed reduction of fecundity and population size within and across generations was likely the result of the downregulation of the reproduction-related vitellogenin gene (CpVg) after exposure to LC30 of LCT and AM. These results provide a better understanding of the overall effects of LCT and AM on C. pomonella and the transgenerational effects which should be taken into consideration when using insecticides in order to control C. pomonella.

Melanoma is an aggressive malignancy with a high mortality rate. Signal transducer and activator of transcription 3 (STAT3), an oncoprotein, is considered as an effective target for treating melanoma. Chrysoeriol is a flavonoid compound, and possesses anti-tumor activity in lung cancer, breast cancer and multiple myeloma; while whether it has anti-melanoma effects is still not known. Chrysoeriol has been shown to restrain STAT3 signaling in an inflammation mouse model.In this study, the anti-melanoma effects of chrysoeriol and the involvement of STAT3 signaling in these effects were investigated.CCK8 assays, 5-ethynyl-2'-deoxyuridine (EdU) staining, Annexin V-FITC/PI staining, Western blot analyses of cleaved caspase-9 and wound healing assays were used to study the anti-melanoma effects of chrysoeriol in cell models. A B16F10 melanoma bearing mouse model was used to evaluate the in vivo anti-melanoma effects of chrysoeriol. Indicators of cell proliferation, cell apoptosis and angiogeneis in melanoma tissues were detected by immunohistochemistry (IHC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Immune cells in melanoma tissues were analyzed by flow cytometry. STAT3-overactivated cell models were used to investigate the involvement of STAT3 signaling in the anti-melanoma effects of chrysoeriol. Molecular dynamics (MD) simulations and surface plasmon resonance (SPR) assays were conducted to determine whether chrysoeriol binds to Src, an upstream kinase of STAT3.The results of cell experiments showed that chrysoeriol dose-dependently inhibited viability, proliferation and migration of, and induced apoptosis in, A375 and B16F10 melanoma cells. Chrysoeriol inhibited the phosphorylation of STAT3, and downregulated the expression of STAT3-target genes involved in melanoma growth and metastasis. Mouse studies showed that chrysoeriol restrained melanoma growth and tumor-related angiogenesis, and altered compositions of immune cells in melanoma microenvironment. Chrysoeriol also inhibited STAT3 signaling in B16F10 allografts. Chrysoeriol's viability-inhibiting effects were attenuated by over-activating STAT3 in A375 cells. Furthermore, chrysoeriol bound to the protein kinase domain of Src, and suppressed Src phosphorylation in melanoma cells and tissues.This study, for the first time, demonstrates that chrysoeriol has anti-melanoma effects, and these effects are partially due to inhibiting STAT3 signaling. Our findings indicate that chrysoeriol has the potential to be developed into an anti-melanoma agent.

This article proposes a novel hybrid rotor permanent magnet (HRPM) machine for the performance of torque and overload capability with the constraint of the rotor diameter. In order to optimize the electromagnetic performance, an analytical model (AM) is built by the magnetic equivalent circuit (MEC) of the rotor and stator considering the saturation and leakage flux effect. A good prediction accuracy is verified by the finite element method (FEM), even in high saturation condition. Based on the AM, the characteristics of the hybrid magnetic pole rotor are analyzed by the equivalent strategy that equivalent PM remanence and thickness of single pole in rotor. Furthermore, a response surface method (RSM) for multi-variate and multi-objective optimization is adapted to improve the electromagnetic performance because of the high torque density and PM material utilization. Finally, a comparison of the torque, PM eddy current loss and anti-demagnetization performance is investigated among surface-mount PM (SPM) machine, spoke-type PM (STPM) machine and HRPM machine. The comparison results show the hybrid PM rotor machine enhances higher torque density and overload capability. Finally, a 12 slot/10 pole HRPM machine is prototyped and tested to validate the analyses.

Over the last decade, quantum computing has experienced significant changes and captured worldwide attention. In particular, superconducting qubits have become the leading candidates for scalable quantum computers, and a number of cryogenic materials have scientifically demonstrated their potential uses in constructing qubit chips. However, because of insufficient coherence time, establishing a robust and scalable quantum platform is still a long-term goal. Another consideration is the control circuits essential to initializing, operating and measuring the qubits. To keep noise low, control circuits in close proximity to the qubits require superior reliability in the cryogenic environment. The realization of the quantum advantage demands qubits with appropriate circuitry designs to maintain long coherence times and entanglement. In this work, we briefly summarize the current status of cryogenic materials for qubits and discuss typical cryogenic circuitry designs and integration techniques for qubit chips. In the end, we provide an assessment of the prospects of quantum computers and some other promising cryogenic materials.

Primary liver cancer is a lethal cancer. The phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway has been implicated in the pathogenesis of liver cancer. Gomisin N (GN), a lignan isolated from the dried fruits of Schisandra chinensis (Turca.) Baill., has been reported to reduce viability of, and induce apoptosis in, HepG2 liver cancer cells. In preadipocytes, GN was found to inhibit Akt activity. In the present study, Akt signaling-related anti-liver cancer mechanisms of GN were investigated. We confirmed that GN reduces cell viability of, and triggers apoptosis in, more liver cancer cell lines. Mechanistic studies revealed that GN lowers protein levels of phospho-PI3K (p85 tyrosine (Tyr)458), phospho-Akt (serine (Ser)473), and Akt downstream molecules Mcl-1 in HepG2 and HCCLM3 cells. Meanwhile, GN activates mTOR and inhibits ULK1 (a negative downstream effector of mTOR) activities. Activation of mTOR has been reported to suppress ULK1 activity and repress autophagy. Indeed, we observed that GN inhibits autophagy in liver cancer cells. In summary, we for the first time demonstrated that GN inhibits the PI3K-Akt pathway and regulates the mTOR-ULK1 pathway in liver cancer cells.

Through rock mechanics test, similar simulation experiment, borehole photographic observation of rock fissure, numerical simulation calculation of plastic zone distribution and deformation monitoring of rock mass during undersea mining, the fractal evolution mechanisms of rock fracture in undersea metallic deposits of Sanshandao Gold Mine were studied by fractal theory. The experimental researches on granite mechanics test in undersea deposit indicate that with the increase of load, the granite deformation energy and the fractal dimension of acoustic emission (FDAE) increase gradually. However, after reaching the peak stress of specimen, the fractal dimensions of acoustic emission (FDAEs) decrease and the granite specimen fails. Therefore, the fractal dimension evolution of rock failure can be divided into four stages, which are fissure inoculation stage, fissure growth stage, fissure expansion stage and fracture instability stage, respectively. By calculating and analyzing the damage photographs of rock specimens in Sanshandao Gold Mine, the fractal dimension of rock fissure is 1.4514, which is close to the average value of FDAE during granite destruction, i.e., 1.4693. Similar simulation experiments of undersea mining show that with the excavation proceeding, the FDAE in rock stratum increases gradually, and when the thickness of the isolation roof is less than 40 m, the FDAE begins to decrease, and meanwhile the sign of water inrush emerges. The numerical simulation researches on the plastic zone distribution of undersea mining in Sanshandao Gold Mine indicate that the fractal dimension of plastic zone (FDPZ) where the failure characteristics occur is 1.4598, close to the result of similar simulation experiment of 1.4364, which shows the sign of water inrush. Meanwhile, the thickness of the isolation roof for undersea mining should be more than 40 m, which is consistent with the results of similar simulation experiment. In Sanshandao Gold Mine, the rock fissures in undersea mining were observed by borehole photography and the rock mass deformation was monitored by multi-point displacement meters, and at the same time the fractal dimensions of strata borehole fissure distribution and energy release ratio (ERR) of rock mass were calculated by fractal principle, which are 1.2328 and 1.2685, respectively. The results demonstrate that rock deformation and fissure propagation are both in the second stage of fissure growth, and have not reached the fourth stage of fracture instability. Therefore, the conclusion can be obtained that the undersea mining in Sanshandao Gold Mine is safe at present.

The hot deformation behavior of a Ta-particle reinforced TiAl composite was studied. Ti–48Al–2Cr–2Nb– 0.2W(at.%)/20vol.%Ta metal matrix composite was fabricated by spark plasma sintering. The deformation behavior was investigated by hot compression tests at the temperature ranging from 1050 to 1200 °C and the strain rate ranging from 1×10−3 to 1 s−1. The constitutive equation containing true strain variables was established. The values of activation energy Q under different strain degrees are between 240 and 280 kJ/mol, which are lower than that of pure TiAl. Based on dynamic material modeling, the processing maps at various strain degrees were established, and the optimized parameters for hot working are 1050–1100 °C and 0.005–0.01 s−1. The microstructural evolution during deformation was characterized, which indicated that the dynamic recrystallization plays an important role in this process.

This paper proposes two novel hybrid rotors permanent magnet (PM) machines for the high torque density in short duration condition operation. In order to enhance the torque performance, the flux concentrated structure of spoke-type PM is employed to increase the air-gap flux density. Meanwhile, the non-magnetic connector of the rotor is employed to eliminate the magnetic flux leakage. The rotors of the conventional machines and the proposed machines are optimized by the finite element analysis (FEA). Furthermore, based on the comparisons of electromagnetic performances for the optimized machines, including the open-circuit flux density, torque, PM eddy current loss, overload capability, the characteristics of the proposed machines are analyzed. The results indicate that the proposed machine can improve the torque at rated and overload operation with growth rate 14.3% and 13.1%, respectively. Finally, a 12-slots/10-pole PM machine is prototyped and FEA is to be validated.

We propose an implementation of a generalized Su-Schrieffer-Heeger (SSH) model based on optomechanical arrays. The topological properties of the generalized SSH model depend on the effective optomechanical interactions enhanced by strong driving optical fields. Three phases including one trivial and two distinct topological phases are found in the generalized SSH model. The phase transition can be observed by turning the strengths and phases of the effective optomechanical interactions via adjusting the external driving fields. Moreover, four types of edge states can be created in generalized SSH model of an open chain under single-particle excitation, and the dynamical behaviors of the excitation in the open chain are related to the topological properties under the periodic boundary condition. We show that the edge states can be pumped adiabatically along the optomechanical arrays by periodically modulating the amplitude and frequency of the driving fields. The generalized SSH model based on the optomechanical arrays provides us a tunable platform to engineer topological phases for photons and phonons, which may have potential applications in controlling the transport of photons and phonons., Comment: 11 pages, 14 figures

Background. Elevated platelet volume is the risk factor for the development and poor overall survival of colorectal cancer (CRC) patients. Both microsatellite status and platelet glycoprotein Ibα (GPIbα) are related to platelet volume in CRC patients. This study aimed to investigate platelet GPIbα ectodomain (termed glycocalicin) levels among CRC patients and the association between the glycocalicin levels and microsatellite status in CRC. Methods. The clinical and laboratory data of 430 CRC patients between January 2018 and December 2018 in Harbin Medical University Cancer Hospital were collected. The microsatellite status was determined with a polymerase chain reaction. The participants were separated into high microsatellite instability (MSI-H) and microsatellite stable (MSS) groups according to microsatellite status. The glycocalicin levels were measured with an enzyme-linked immunosorbent assay, and the cut-off point was determined with the receiver-operating characteristics curve. The clinical and pathological characteristics were collected via electronic medical records. Logistic regression was used to explore the association between glycocalicin and microsatellite status. Results. Among the 430 CRC patients enrolled, 64 patients (14.9%) were identified as MSI-H and others as MSS CRC. Glycocalicin levels were significantly reduced in patients with MSI-H than those with MSS. After controlling for potential confounders, logistic regression analysis revealed that glycocalicin levels were independently associated with MSI-H CRC. Conclusions. Reduced glycocalicin levels are associated with the MSI-H subtype of CRC. Further research is needed to elucidate the mechanisms of the association between glycocalicin and MSI-H in CRC patients.

Angiogenesis plays an important role in the growth and metastasis of solid tumors including melanoma. Inhibiting tumor-associated angiogenesis is a tactic in treating melanoma. Dioscin restrains angiogenesis in colon tumor and has anti-melanoma effects in cell and animal models. In a previous study, we found that dioscin inhibits Src/STAT3 signaling in melanoma cells. Activation of the Src/STAT3 pathway has been shown to promote tumor angiogenesis. This study aimed to determine whether dioscin's anti-melanoma effects is related to inhibiting Src/STAT3 signaling-mediated angiogenesis. In a B16F10 allograft mouse model, we found that dioscin inhibited melanoma growth and angiogenesis. To exclude the impact of tumor growth on angiogenesis, a chicken chorioallantoic membrane (CAM) model was used to verify the anti-angiogenic effect of dioscin. Results showed that dioscin suppressed vessel formation in CAM. To determine if tumor secreted pro-angiogenic cytokines are involved in the anti-angiogenic effect of dioscin, conditioned media from dioscin-treated A375 melanoma cells were used to culture human umbilical vein endothelial cells (HUVECs), and tube formation was monitored. It was observed that the tube formation of HUVECs was inhibited. Mechanistic studies revealed that dioscin inhibited the activation of Src and STAT3, and lowered mRNA and protein levels of STAT3 transcriptionally-regulated genes, in B16F10 melanomas. ELISA assays showed that dioscin decreased the secretion of MMP-2, MMP-9 and VEGF from A375 cells. Over-activation of STAT3 lessened the effects of dioscin in decreasing the secretion of pro-angiogenic cytokines from melanoma cells, and in inhibiting tube formation of HUVECs cultured with conditioned media from melanoma cell cultures. In summary, we for the first time demonstrated that inhibiting Src/STAT3 signaling-mediated angiogenesis is involved in the anti-melanoma effects of dioscin. This study provides further pharmacological groundwork for developing dioscin as an anti-melanoma agent.

Background Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor and second most common cause of tumor-related deaths worldwide. Activated platelets play a prominent role in tumor. Platelet distribution width (PDW) indicates platelets activation and is altered in malignancies. The aim of this study was to explore the prognostic value of PDW for overall survival (OS) in HCC patients. Methods We retrospectively reviewed 273 HCC patients at a single institution from 2010 to 2014. The relationship between PDW and clinicopathological characteristics was analyzed. Kaplan-Meier curves and multivariate Cox regression analyses were used to evaluate the relationship of PDW with OS. Results Low PDW levels were observed in 127 (46.5%) out of 273 patients. A significant correlation was found between PDW and liver cirrhosis. Median follow-up was 36 months, survival curves revealed that the patients with increased PDW had significantly shorter survival time than those with normal PDW (p= 0.001). Cox regression analysis demonstrated that PDW was an independent prognostic factor for overall survival (hazard ratio, 2.464; 95% confidence interval [CI], 1.402-4.330, p= 0.001). Conclusion PDW is significantly associated with OS in HCC. This result suggests activated platelet may affect clinical outcome and warrant continued investigation.

This paper presents an analytical method for predicting the electromagnetic performance in permanent magnet (PM) machine with the spoke-type rotor (STR) and a proposed hybrid rotor structure (HRS), respectively. The key of this method is to combine magnetic field analysis model (MFAM) with the magnetic equivalent circuit model. The influence of the irregular PM shape is considered by the segmentation calculation. To obtain the boundary condition in the MFAM, respectively, two equivalent methods on the rotor side are proposed. In the STR, the average flux density of the rotor core outer-surface is calculated to solve the Laplace's equation with considering for the rotor core outer-surface eccentric. In the HRS, based on the Thevenin's theorem, the equivalent parameters of PM remanence BreB and thickness hpme are obtained as a given condition, which can be utilized to compute the air-gap flux density by conventional classic magnetic field analysis model of surface-mounted PMs with air-gap region. Finally, the proposed analytical models are verified by the finite element analysis (FEA) with comparisons of the air-gap flux density, flux linkage, back-EMF and electromagnetic torque, respectively. Furthermore, the performance that the machine with the proposed hybrid structure rotor can improve the torque density as explained.

The interaction between the quantum emitter and topological photonic system makes both the emitter and the photon behave in exotic ways. We here study a system that a giant atom is coupled to two points of a one-dimensional topological waveguide formed by the Su-Schrieffer-Heeger (SSH) chain. The topological nature of the hybrid system is studied. We find that the giant atom can act as an effective boundary and induce the chiral zero energy modes for the waveguide under the periodical boundary. The properties of these modes are similar to those in the SSH model with open boundary. Meanwhile, the SSH waveguide, as a structured environment, induces the retarded effect and the non-Markovian dissipation of the giant atom. Our work may promote more studies on the interaction between matter and topological environment. Experimental demonstration for our study using superconducting quantum circuits is very possible within current technology., 21 Pages, 20 Figures

The identification of time-varying parameters (e.g., directly inaccessible in situ signals in vacuum and low-temperature environments) is prevalent for characterizing the dynamics of quantum processes. Under certain circumstances, they can be identified from time-resolved measurements via Ramsey interferometry experiments, but only with specially designed probe systems can the parameters be explicitly read out, and a rigorous identifiability analysis is lacking, i.e., whether the measurement data are sufficient for unambiguous identification. In this paper we formulate this problem as the invertibility of the input-output mapping associated with the quantum system for which an algebraic identifiability criterion is derived based on the system's relative degree. The invertibility analysis also leads to an inversion-based algorithm for numerically identifying the parameters, which is computationally much more efficient than nonlinear regression methods. The effectiveness of the criterion are demonstrated by numerical examples.

Background and purpose Pancreatic cancer is an exceptionally fatal disease. However, therapeutic drugs for pancreatic cancer have presented a serious shortage over the past few decades. Signal transducer and activator of transcription-3 (STAT3) is persistently activated in many human cancers where it promotes tumour development and progression. Natural products serve as an inexhaustible source of anticancer drugs. Here, we identified the natural product trienomycin A (TA), an ansamycin antibiotic, as a potential inhibitor of the STAT3 pathway with potent activity against pancreatic cancer. Experimental approach Effects of trienomycin A on transcriptional activity of STAT3 were assessed by the STAT3-luciferase (STAT3-luc) reporter system. In vitro and in vivo inhibitory activity of TA against pancreatic cancer made use of molecular docking, surface plasmon resonance (SPR) assay, MTS assay, colony formation assay, transwell migration/invasion assay, flow cytometric analysis, immunofluorescence staining, quantitative real-time polymerase chain reaction (PCR), western blotting, tumour xenograft model, haematoxylin and eosin (H&E) staining and immunohistochemistry. Key results Trienomycin A directly bound to STAT3 and inhibited STAT3 (Tyr705) phosphorylation, thus inhibiting the STAT3 pathway. Trienomycin A also inhibited colony formation, proliferation, migration and invasion of pancreatic cancer cell lines. Trienomycin A also markedly blocked pancreatic tumour growth in vivo. More importantly, trienomycin A did not show obvious toxicity at the effective dose in mice. Conclusions and implications Trienomycin A exerted anti-neoplastic activity by suppressing STAT3 activation in pancreatic cancer. This natural product could be a novel therapeutic candidate for pancreatic cancer.

The unc-13 homolog B (UNC13B) gene encodes a presynaptic protein, mammalian uncoordinated 13-2 (Munc13-2), which is highly expressed in the brain—predominantly in the cerebral cortex—and plays an essential role in synaptic vesicle priming and fusion, potentially affecting neuronal excitability. However, the functional significance of the UNC13B mutation in human disease is not known. In this study, we screened for novel genetic variants in a cohort of 446 unrelated cases (families) with partial epilepsy without acquired causes by trio-based whole-exome sequencing. UNC13B variants were identified in 12 individuals affected by partial epilepsy and/or febrile seizures from eight unrelated families. The eight probands all had focal seizures and focal discharges in EEG recordings, including two patients who experienced frequent daily seizures and one who showed abnormalities in the hippocampus by brain MRI; however, all of the patients showed a favourable outcome without intellectual or developmental abnormalities. The identified UNC13B variants included one nonsense variant, two variants at or around a splice site, one compound heterozygous missense variant and four missense variants that cosegregated in the families. The frequency of UNC13B variants identified in the present study was significantly higher than that in a control cohort of Han Chinese and controls of the East Asian and all populations in the Genome Aggregation Database (gnomAD). Computational modelling, including hydrogen bond and docking analyses, suggested that the variants lead to functional impairment. In Drosophila, seizure rate and duration were increased by Unc13b knockdown compared to wild-type flies, but these effects were less pronounced than in sodium voltage-gated channel alpha subunit 1 (Scn1a) knockdown Drosophila. Electrophysiological recordings showed that excitatory neurons in Unc13b-deficient flies exhibited increased excitability. These results indicate that UNC13B is potentially associated with epilepsy. The frequent daily seizures and hippocampal abnormalities but ultimately favourable outcome under anti-epileptic therapy in our patients indicate that partial epilepsy caused by UNC13B variant is a clinically manageable condition., Wang et al. present clinical and experimental evidence suggesting that UNC13B is a novel epilepsy gene. They describe UNC13B mutations in 12 individuals affected by partial epilepsy and/or febrile seizures from eight unrelated families, and show seizure-like behaviour and increased neural firing in Unc13b knockdown flies.

We study the phase controlled transmission properties in a compound system consisting of a 3D copper cavity and an yttrium iron garnet (YIG) sphere. By tuning the relative phase of the magnon pumping and cavity probe tones, constructive and destructive interferences occur periodically, which strongly modify both the cavity field transmission spectra and the group delay of light. Moreover, the tunable amplitude ratio between pump-probe tones allows us to further improve the signal absorption or amplification, accompanied by either significantly enhanced optical advance or delay. Both the phase and amplitude-ratio can be used to realize in-situ tunable and switchable fast-slow light. The tunable phase and amplitude-ratio lead to the zero reflection of the transmitted light and an abrupt fast-slow light transition. Our results confirm that direct magnon pumping through the coupling loops provides a versatile route to achieve controllable signal transmission, storage, and communication, which can be further expanded to the quantum regime, realizing coherent-state processing or quantum-limited precise measurements., Comment: 24 pages, 5 figures

Supplemental material, Online supplementary file 1, for Chemical Profile Assessment and Potential Bioactive Component Screening of a Chinese Patent Herbal Drug Yi-Shen-Hua-Shi Granule by Chan Yuen-Cheung, Zhao Jing, Hu Qin, Guo Hui, Liu Yu-Xi, Wu Jia-Ying, Zheng Zhao-Guang and Yu Zhi-Ling in Natural Product Communications

Primary liver cancer is a lethal cancer. The phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway has been implicated in the pathogenesis of liver cancer. Gomisin N (GN), a lignan isolated from the dried fruits of Schisandra chinensis (Turca.) Baill., has been reported to reduce viability of, and induce apoptosis in, HepG2 liver cancer cells. In preadipocytes, GN was found to inhibit Akt activity. In the present study, Akt signaling-related anti-liver cancer mechanisms of GN were investigated. We confirmed that GN reduces cell viability of, and triggers apoptosis in, more liver cancer cell lines. Mechanistic studies revealed that GN lowers protein levels of phospho-PI3K (p85 tyrosine (Tyr)458), phospho-Akt (serine (Ser)473), and Akt downstream molecules Mcl-1 in HepG2 and HCCLM3 cells. Meanwhile, GN activates mTOR and inhibits ULK1 (a negative downstream effector of mTOR) activities. Activation of mTOR has been reported to suppress ULK1 activity and repress autophagy. Indeed, we observed that GN inhibits autophagy in liver cancer cells. In summary, we for the first time demonstrated that GN inhibits the PI3K-Akt pathway and regulates the mTOR-ULK1 pathway in liver cancer cells.

Background: Postoperative sepsis in cancer patients becomes a major problem at present, but the efficiently prognostic biomarkers are limited. The present study was sought to evaluate the prognostic relevance of absolute lymphocyte counts (ALCs) in cancer patients with postoperative sepsis, which might help patients to get early treatment and improve their prognosis.Methods: Retrospective study was conducted under 368 cancer patients with postoperative sepsis who were admitted in ICU of two Chinese tertiary care hospitals from January 1, 2016 to December 31, 2017. ALCs were daily collected during the first week after being enrolled in the study. The primary outcomes of the study included 28-day and 90-day mortalities, while the secondary outcomes were hospital and ICU length of stay.Results: The absolute lymphocyte counts on day 3 were reduced in the survivors comparing with those in non-survivors. Statistically, the significantly decreased 28-day and 90-day survival rates were detected in the patients with severe and moderate lymphopenia, compared to those with no lymphopenia. These present results were consistently found and evidently confirmed in the two different hospitals.Conclusions: In accordance with the day-4 lymphopenia prediction of sepsis diagnosis, this present study revealed that lymphopenia on the day 3 after the diagnosis of sepsis was able to predict the early mortality in postoperative cancer patients. Earlier monitoring and management of lymphopenia may be needed for cancer patients with postoperative sepsis.

Background Herba Siegesbeckiae (HS), the dried aerial parts of Siegesbeckia orientalis L., S. pubescens Makino, or S. glabrescens Makino, is traditionally used for treating chronic diseases in China. However, there is no information about the chronic toxicity of HS. The objective of this study is to evaluate the 24-week oral dosing toxicities of HS aqueous extract (HSE) in rats. Methods S. orientalis-originated HS was reflux-extracted with distilled water. Sprague–Dawley rats were randomly divided into four groups, with 10 males and 10 females in each group. The rats were intragastrically administered with HSE at 5, 1.67 and 0.56 g/kg (experimental groups) or an equal volume of distilled water (control group), 6 days a week, for 24 weeks. The high dose of HSE (5 g/kg) was its maximum tolerated dose. Body weight was recorded every 2 days during the experimental period. Chemical, hematological and histopathological parameters, as well as organ weights, were measured at the end of the experiment. Results Decreased body weight gain; increased liver and lung relative weights; histopathological alterations in liver and lung tissues; elevated serum levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase were found after HSE treatments. In liver tissues, HSE treatment upregulated levels of three pro-inflammatory cytokines: IL-6, IL-1β and TNF-α. In lung tissues, HSE treatment caused oxidative stress and activated mitogen-activated protein kinases (MAPKs). Conclusion Long-term oral administration of HSE caused toxicities in rats evidenced by decreased body weight gain, as well as liver and lung damage. Treatment-induced oxidative stress, inflammation and MAPK activation are involved in HSE’s toxicities. Caution should be taken when using HS to treat chronic diseases.

Fibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. A standardized ethanolic extract of RL (RLE) has been shown to exert anti-arthritic effects in collagen-induced arthritis (CIA) rats. Some constituents of RLE were reported to inhibit JAK2/STAT3 signaling in rat FLS. Here, we determined whether RLE inhibits FLS hyperproliferation, and explored the involvement of STAT3 signaling in this inhibition. In joints of CIA rats, RLE increased apoptotic FLS. In IL-6/sIL-6R-stimulated RA-FLS, RLE reduced cell viability and evoked cell apoptosis. In synovial tissues of CIA rats, RLE lowered the protein level of phospho-STAT3. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited activation/phosphorylation of STAT3 and JAK2, decreased the nuclear localization of STAT3, and downregulated protein levels of Bcl-2 and Mcl-1. Over-activation of STAT3 diminished RLE’s anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS. In summary, RLE inhibits hyperproliferation of FLS in rat and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug.

Malignant melanoma is aggressive and has a high mortality rate. Toll-like receptor 4 (TLR4) has been linked to melanoma growth, angiogenesis and metastasis. However, signal transduction mediated by TLR4 for driving melanoma progression is not fully understood. Signal transducer and activator of transcription 3 (STAT3) has been identified as a major oncogene in melanoma progression. We found: that TLR4 expression positively correlates with activation/phosphorylation of STAT3 in human melanoma samples; that TLR4 ligands activate STAT3 through MYD88 and TRIF in melanoma cells; and that intratumoral activation of TLR4 increases STAT3 activation in the tumor and promotes tumor growth, angiogenesis, epithelial–mesenchymal transition (EMT) and the formation of an immunosuppressive tumor microenvironment in mice. Further, we found that the effects mediated by activating TLR4 are weakened by suppressing STAT3 function with a dominant negative STAT3 variant in melanoma. Collectively, our work identifies STAT3 activation as a key event in TLR4 signaling-mediated melanoma progression, shedding new light on the pathophysiology of melanoma.

As the counterpart of $\mathcal{P}\mathcal{T}$ symmetry, for anti-$\mathcal{P}\mathcal{T}$-symmetry abundant phenomena and potential applications have been predicted or demonstrated theoretically. However, experimental realization of the coupling required in anti-$\mathcal{P}\mathcal{T}$ symmetry is difficult. By our coupling two yttrium iron garnet spheres commonly to a microwave cavity, the large cavity dissipation rate makes the magnon-magnon coupling dissipative and purely imaginary. Thereby, the hybrid magnon-cavity system obeys a two-dimensional anti-$\mathcal{P}\mathcal{T}$ Hamiltonian. In terms of the magnon-readout method, the method adopted here, we demonstrate the validity of our method in constructing an anti-$\mathcal{P}\mathcal{T}$ system and present the counterintuitive level-attraction process. Our work provides a platform to explore the anti-$\mathcal{P}\mathcal{T}$-symmetry properties and paves the way to study dynamical evolution and topological properties around exceptional points in multimagnon-cavity systems.

Ethnopharmacology relevance Si-Jun-Zi-Tang (SJZT) is a traditional Chinese medicine formula used to treat chronic and debilitating diseases including melanoma. SJZT-based therapies have achieved good clinical outcomes in melanoma management. However, the pharmacological basis of SJZT for its clinical use in melanoma treatment is not fully understood. Aim of the study To investigate the anti-melanoma effects and mechanism of action of an ethanolic extract of SJZT. Materials and methods SJZT was extracted using 50% ethanol. A murine B16 melanoma-bearing mouse model was employed to investigate the anti-melanoma effects of SJZT. microRNA (miRNA) and mRNA levels were examined by RT-qPCR, and protein levels were measured by Western blotting. Results SJZT significantly inhibited B16 tumor growth in mice. Mechanistic investigations revealed that SJZT elevated miR-34b (a tumor suppressing miRNA), and lowered c-Met (a miR-34b target gene) and β-catenin (a downstream molecule of c-Met signaling) expression levels in the B16 tumors. Conclusions In this study we found, for the first time, that SJZT exerts anti-melanoma effects and regulates the miR-34b/c-Met/β-catenin pathway in a melanoma mouse model. Our findings provide pharmacological justifications for the clinical use of SJZT in treating melanoma.

Nonlinear wave–matter interactions may give rise to solitons, phenomena that feature inherent stability in wave propagation and unusual spectral characteristics. Solitons have been created in a variety of physical systems and have had important roles in a broad range of applications, including communications, spectroscopy and metrology1–4. In recent years, the realization of dissipative Kerr optical solitons in microcavities has led to the generation of frequency combs in a chip-scale platform5–10. Within a cavity, photons can interact with mechanical modes. Cavity optomechanics has found applications for frequency conversion, such as microwave-to-optical or radio-frequency-to-optical11–13, of interest for communications and interfacing quantum systems operating at different frequencies. Here we report the observation of mechanical micro-solitons excited by optical fields in an optomechanical microresonator, expanding soliton generation in optical resonators to a different spectral window. The optical field circulating along the circumference of a whispering gallery mode resonator triggers a mechanical nonlinearity through optomechanical coupling, which in turn induces a time-varying periodic modulation on the propagating mechanical mode, leading to a tailored modal dispersion. Stable localized mechanical wave packets—mechanical solitons—can be realized when the mechanical loss is compensated by phonon gain and the optomechanical nonlinearity is balanced by the tailored modal dispersion. The realization of mechanical micro-solitons driven by light opens up new avenues for optomechanical technologies14 and may find applications in acoustic sensing, information processing, energy storage, communications and surface acoustic wave technology. Stable, dissipative optomechanical solitons are realized using optical fields in a whispering gallery mode resonator by balancing the optomechanical nonlinearities with a tailored modal dispersion.

Scanning electron microscope (SEM) was used to observe and analyze the microstructure of the cross section of cortical bone. The observation results illustrated that the cortical bone is composed of cylindrical osteons and interstitial bone between osteons, and the osteon are unevenly distributed. Based on the microstructure characteristics of cortical bone, three types of cortical bone mesoscopic analysis models were established. Then, the extended finite element method (X-FEM) was used to simulate the microcrack propagation process in bone. The simulate results show that the crack initiation strain of the two-phase model is 19.1% larger than that of the single-phase model, and the three-phase model is 57.8% larger than that of the two-phase model, which demonstrated that the osteons and cement line can significantly enhance the crack initiation strain of bone. In addition, under the same boundary conditions, the model with cement line can effectively change the propagation path of microcrack and prevent the propagation of crack. Therefore, the cement lines in cortical bone can effectively increase the fracture resistance of bone and enhance the fracture toughness of cortical bone.

We propose to periodically modulate the onsite energy via two-tone drives, which can be furthermore used to engineer artificial gauge potential. As an example, we show that the fermionic ladder model penetrated with effective magnetic flux can be constructed by superconducting flux qubits using such two-tone-drive-engineered artificial gauge potential. In this superconducting system, the single-particle ground state can range from vortex phase to Meissner phase due to the competition between the interleg coupling strength and the effective magnetic flux. We also present the method to experimentally measure the chiral currents by the single-particle Rabi oscillations between adjacent qubits. In contrast to previous methods of generating artifical gauge potential, our proposal does not need the aid of auxiliary couplers and in principle remains valid only if the qubit circuit maintains enough anharmonicity. The fermionic ladder model with effective magnetic flux can also be interpreted as one-dimensional spin-orbit-coupled model, which thus lay a foundation towards the realization of quantum spin Hall effect.

Toward quantum machine learning deployed on imperfect near-term intermediate-scale quantum (NISQ) processors, the entire physical implementation of should include as less as possible hand-designed modules with only a few ad-hoc parameters to be determined. This work presents such a hardware-friendly end-to-end quantum machine learning scheme that can be implemented with imperfect near-term intermediate-scale quantum (NISQ) processors. The proposal transforms the machine learning task to the optimization of controlled quantum dynamics, in which the learning model is parameterized by experimentally tunable control variables. Our design also enables automated feature selection by encoding the raw input to quantum states through agent control variables. Comparing with the gate-based parameterized quantum circuits, the proposed end-to-end quantum learning model is easy to implement as there are only few ad-hoc parameters to be determined. Numerical simulations on the benchmarking MNIST dataset demonstrate that the model can achieve high performance using only 3-5 qubits without downsizing the dataset, which shows great potential for accomplishing large-scale real-world learning tasks on NISQ processors.arning models. The scheme is promising for efficiently performing large-scale real-world learning tasks using intermediate-scale quantum processors., Comment: 10 pages, 6 figures

Topological matter and topological optics have been studied in many systems, with promising applications in materials science and photonics technology. These advances motivate the study of the interaction between topological matter and light, as well as topological protection in light-matter interactions. In this work, we study a waveguide-interfaced topological atom array. The light-matter interaction is nontrivially modified by topology, yielding novel optical phenomena. We find topology-enhanced photon absorption from the waveguide for large Purcell factor, i.e., $\Gamma/\Gamma_0\gg 1$, where $\Gamma$ and $\Gamma_0$ are the atomic decays to waveguide and environment, respectively. To understand this unconventional photon absorption, we propose a multi-channel scattering approach and study the interaction spectra for edge- and bulk-state channels. We find that, by breaking inversion and time-reversal symmetries, optical anisotropy is enabled for reflection process, but the transmission is isotropic. Through a perturbation analysis of the edge-state channel, we show that the anisotropy in the reflection process originates from the waveguide-mediated non-Hermitian interaction. However, the inversion symmetry in the non-Hermitian interaction makes the transmission isotropic. At a topology-protected atomic spacing, the subradiant edge state exhibits huge anisotropy. Due to the interplay between edge- and bulk-state channels, a large topological bandgap enhances nonreciprocal reflection of photons in the waveguide for weakly broken time-reversal symmetry, i.e., $\Gamma_0/\Gamma\ll 1$, producing complete photon absorption. We show that our proposal can be implemented in superconducting quantum circuits. The topology-enhanced photon absorption is useful for quantum detection. This work shows the potential to manipulate light with topological quantum matter., Comment: 15 pages, 8 figures

The breakdown of a vacuum arc under high applied voltage conditions usually occurs on very short time and space scales, and a deep understanding of these processes is essential to extend the application of vacuum arc devices. To study the time and spatial evolution of plasma parameters during vacuum breakdown, a two-dimensional axial-symmetric particle-in-cell code with Monte Carlo collisions is used in the numerical simulation of tip-to-plate electrode configuration. In this simulation, in addition to considering the primary and secondary ionization of copper atoms, the excitation and de-excitation processes of copper atoms are also introduced so that the evolution of the light intensity of the vacuum arc in the different stages of breakdown processes can be obtained by tracking the de-excitation process of the atoms, which can be considered a virtual camera. In this way, the cathode radiance, anode light expansion, arc channel establishment, and arc quenching processes can be visually observed, and the trends are consistent with the images taken by Intensified Charge-Coupled Device (ICCD) and streak cameras reported in the literature. The analysis of the sputtering amount of the anode material due to the impact of the cathode plasma to the anode surface shows that the contribution of atoms, singly, and doubly ionized ions to the sputtering of the anode material varies at different stages of the discharge.

Scallop is popular for its delicious taste and rich nutrition value. This study investigated the metabolomic changes in free amino acid (FAA), 5′-nucleotide, and lipid composition of scallops collected in different seasons. Results showed that the content of the FAA and 5′-nucleotide in summer was significantly higher than in other seasons. Adenosine 5′-monophosphate, glycine, and alanine were dominant from June to August. A total of 176 lipids, including 50 triacylglycerols (TAG), 60 phosphatidylcholines (PC), and 30 phosphatidylethanolamines (PE), were identified in the scallop adductor muscle. PC and PE were dominant from February to June, and TAG was dominant in November. The unsaturation degree of TAG was increased from July to November, and the highest proportion of polyunsaturated phospholipids appeared in August and September. Overall, scallops have high nutritional value in summer. This study is helpful for the development of scallop products with high nutrition and high value.